PROJECT SUMMARY Individuals with body dysmorphic disorder (BDD) misperceive specific aspects of their appearance to be conspicuously flawed or defective, despite these being unnoticeable or appearing miniscule to others. With convictions of disfigurement and ugliness, they typically have poor insight or delusional beliefs, obsessive thoughts and compulsive behaviors, anxiety, and depression. These result in significant difficulties in functioning, depression, suicide attempts (25%), and psychiatric hospitalization (50%). Despite this, relatively few studies of the neurobiology, and few treatment studies, have been conducted. This underscores a critical need for research to identify novel targets for intervention based on a comprehensive understanding of the pathophysiological mechanisms. Neuropsychological, behavioral, and neurobiological research by our group and others have uncovered mechanisms that may contribute to perceptual distortions, including prominent abnormalities in visual processing systems. These have contributed to a model of diminished global/holistic processing and enhanced local/detailed processing, attributed to ?bottom-up? and ?top-down? disturbances in perception. Using psychophysical experiments and novel visual modulation techniques, we have probed the brain?s visual systems responsible for global and local processing and found early evidence that they may be modifiable in BDD. These techniques include a ?top-down? attentional modulation and a ?bottom-up? perceptual modulation strategy. Abnormal eye gaze and emotional arousal when viewing faces may further contribute to abnormal perception. Whether these brain and behavior abnormalities are directly linked to abnormal perception remains to be understood. Accordingly, this study will determine a) if abnormalities in neural activation and connectivity in BDD when viewing one?s appearance are directly associated with abnormalities in perceptual functioning; and b) if changes in neural activation and connectivity from these visual modulation strategies are linked to changes in perceptual functioning, thus representing potential biomarkers. We will also determine how attentional systems, eye gaze behaviors and emotional arousal interact with brain functioning in visual systems, and with global and local perceptual functioning. We will enroll 80 participants with BDD, 40 with subclinical BDD, and 40 healthy controls who will undergo functional magnetic resonance imaging while viewing photographs of their, and others?, faces. We will obtain measures of global and local visual processing, emotional arousal while viewing their face, and eye gaze behaviors using eye tracking. To understand the malleability of global/local perception, and the neural mechanisms of these changes, we will determine whether repeated visual modulation using top-down and bottom-up strategies results in alterations of perceptual functioning and brain activity/connectivity, and relationships between them. Results will provide a comprehensive mechanistic model of abnormal visual information processing underlying the core symptom domain of misperceptions of appearance. This will lay the groundwork for next-step translational approaches.